Abstract
Genetic interaction between donor and recipient may dictate the impending responses after transplantation. In this study, we evaluated the role of the genetic predispositions of stromal-derived factor-1 (SDF1) [rs1801157 (G>A)] and CXC receptor 4 (CXCR4) [rs2228014 (C>T)] on renal allograft outcomes. A total of 335 pairs of recipients and donors were enrolled. Biopsy-proven acute rejection (BPAR) and long-term graft survival were traced. Despite similar allele frequencies between donors and recipients, minor allele of SDF1 rs1801157 (GA+AA) from donor, not from recipients, has a protective effect on the development of BPAR compared to wild type donor (GG) (P = 0.005). Adjustment for multiple covariates did not affect this result (odds ratio 0.39, 95% C.I 0.20–0.76, P = 0.006). CXCR4 rs2228014 polymorphisms from donor or recipient did not affect the incidence of acute rejection. SDF1 was differentially expressed in renal tubular epithelium with acute rejection according to genetic variations of donor rs1801157 showing higher expressions in the grafts from GG donors. Contrary to the development of BPAR, the presence of minor allele rs1801157 A, especially homozygocity, predisposed poor graft survival (P = 0.001). This association was significant after adjusting for several risk factors (hazard ratio 3.01; 95% C.I = 1.19–7.60; P = 0.020). The allelic variation of recipients, however, was not associated with graft loss. A donor-derived genetic polymorphism of SDF1 has influenced the graft outcome. Thus, the genetic predisposition of donor should be carefully considered in transplantation.
Highlights
A variety of recently discovered potent immunosuppressive agents have significantly improved short-term renal allograft survival in the last two decades
CXC receptor 4 (CXCR4) rs2228014 polymorphisms from donor or recipient did not affect the incidence of acute rejection. (Table 2, 3) When we examined 57 acute cellular rejection pathologic findings according to donor Stromal-derived factor-1 (SDF1) rs1801157 genetic variations (GG, n = 43; GA, n = 13; AA, n = 1), there were no significant differences between the polymorphism and severity of acute rejection (Table S1)
Our analysis identified a statistically significant association between the rs1801157 genetic variation at 3’ UTR of SDF1 and graft outcome in terms of Biopsyproven acute rejection (BPAR) and graft loss after kidney transplantation
Summary
A variety of recently discovered potent immunosuppressive agents have significantly improved short-term renal allograft survival in the last two decades. Various immunological and non-immunological factors may affect the outcome of an allograft, the genetic interactions between donors and recipients may be an important aspect for the impending responses after organ transplantation. We demonstrated genetic interactions of the CCR5 cytokine between donors and recipients and its effects on allograft rejection and allograft survival [1]. Acute rejection (AR) and subsequent chronic inflammatory processes are initiated by the presentation of donor-antigens to recipient T cells, they are the ultimate manifestations of active interactions between grafts and recipients that mobilize various types of cells and humoral factors. Genetic polymorphism of SDF1 has been reported to have an effect on the expression of SDF1 [3,4] and affects patient survival in liver transplantation [5]. The role of SDF1 expression controlled by genetic polymorphisms has not been investigated thoroughly in the transplantation field
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